Atrioventricular (AV) valves are cardiac valves that prevent backflow from the ventricles into the atria during systole. They are anchored to the wall of the heart at the fibrous skeleton by anchoring tendons named chordae tendineae. The chordae tendineae are attached to papillary muscles. Together, the papillary muscles and the chordae tendineae keep the valves from prolapsing into the atria when they close during systole. The actual opening and closing of the valves is caused by the pressure gradient across the valve. The left side AV valve is a bicuspid valve having two flaps or leaflets, and is commonly known as the mitral valve due to its shape being reminiscent of a bishop's mitre. The right side AV valve is a tricuspid valve, having three flaps or leaflets. Both of these valves may be damaged and dysfunctional, resulting in leakage during systole, requiring the valves to be repaired or replaced.
While the mitral valve is generally an ellipse or D-shaped, the tricuspid valve is more circular. The left ventricle pumps oxygenated blood around the body and so the mitral valve has to withstand a much higher pressure than the tricuspid valve which only has to pump deoxygenated blood to the nearby lungs. Mitral valve regurgitation causes heart murmurs and may have severe physiological consequences.
Occasionally, the mitral valve is congenitally abnormal or destroyed by infection or a bacterial endocarditis. More often the mitral valve becomes degenerative with age or as a result of rheumatic fever. There are different valvular heart disorders associated with the mitral valve such as mitral stenosis and mitral regurgitation,
In the case of mitral stenosis, the valve orifice, i.e. the cross-section available for blood passage is reduced because of calcium nodes, leaflet thickening and/or reduced leaflet mobility, and, consequently, the valve does not allow normal blood flow. To overcome the damaged valve and too transport the same amount of blood, the left atrium requires a higher pressure than normal.
The constant pressure overload of the left atrium may cause it to increase in size and become more prone to develop atrial fibrillation and to lose the atrial kick. The loss of the atrial kick due to atrial fibrillation can cause a precipitous decrease in cardiac output. A reduction in cardiac output, associated with acceleration of heart rate and shortening of the diastolic time, frequently leads to congestive heart failure.
In most cases mitral stenosis is due to rheumatic heart disease. The treatment options for mitral stenosis include medical management, surgical repair, surgical replacement of the valve, and percutaneous balloon valvuloplasty.
Mitral regurgitation MR is caused either by ischemic heart disease (Ischemic MR) or mitral valve prolapse (also referred to as degenerative myxomotous)—(hereinafter MVP). Ischemic MR is a result of ventricular remodeling which is secondary to ischemic heart disease. The heart's posterior wall, which is not attached to the heart's fibrous skeleton, dilates. As a result of the change of the left ventricular geometry, the posterior leaflet, which is attached to the posterior heart wall, is displaced and misaligned from the anterior leaflet which results in mitral regurgitation.
MVP is a condition caused by degeneration of the valve's connective tissue. Patients with classic MVP have surplus connective tissue. This weakens the leaflets and adjacent tissue, resulting in increased leaflet area and elongation of the chordae tendineae. Elongation of the chordae tendineae often causes rupture. Tweaked leaflets may be displaced in some portion of one or both of the abnormally thickened mitral valve leaflets into the left atrium during systole. Advanced lesions lead to leaflet folding, inversion, and displacement toward the left atrium. The abnormal leaflet structure leads to incomplete closure of the mitral valve and MR.
In mitral regurgitation, the heart has to work harder by pumping not only the regular volume of blood, but also the extra volume of blood that is regurgitated back into the left atrium. The added workload creates an excessive strain on the left ventricle, which can lead to heart failure.
While patients with mild to moderate mitral regurgitation caused by MVP might experience no symptoms, increasing severity, even without symptoms, increases the load on the left ventricle. Over time this can result in ventricular dilatation and congestive heart failure.
Mitral valve disease is conventionally treated by open heart surgery; either by surgical repair usually with an annuloplasty ring or by surgical replacement with valve prosthesis. There are some advantages to repairing a mitral valve rather than replacing it, especially in mild cases and in asymptomatic patients of MVP. Some studies suggest a lower mortality at the time of operation, a significantly lower risk of stroke, a lower rate of infection and improved long-term survival with mitral valve repair.
In some cases, such as when the valve is too damaged, mitral valves may require replacement.
Charles Hufnagel, a professor of experimental surgery at Georgetown University, developed an artificial heart valve and performed the first artificial valve implantation surgery in a human patient. The valve was a methacrylate ball in a methacrylate aortic-sized tube which did not replace the leaky valve but acted as an auxiliary valve. The first replacement valve surgeries were performed in 1960 by two surgeons who developed their ball-in-cage designs independently. Dwight Harken developed a double-cage design in which the outer cage separates the valve struts from the aortic wall. At the University of Oregon, Albert Starr, working with electrical engineer Lowell Edwards, designed a silicone ball inside a cage made of stellite-21, an alloy of cobalt, molybdenum, chromium, and nickel. The Starr-Edwards heart valve is still in use today.
A percutaneous heart valve implantation method was later developed by Edwards Lifesciences PVT Ltd. and is described in U.S. Pat. No. 6,730,118, which is herein incorporated by reference in its entirety. The main idea behind this method is implantation inside the stenotic region of a calcified native valve without removing the native valve. This method stents the stenotic valve open and uses it as an attachment means.
There are two primary types of artificial mitral valves: (i) ceramic or mechanical valves and (ii) tissue or biological valves. The so-called mechanical valves are currently made entirely from metal and/or pyrolytic carbon and are long-lasting. Mechanical valves, although durable, require lifelong anticoagulation drugs. Currently available mechanical valves come in several different designs, including single and double flap valves, and are manufactured by well-known companies such as St. Jude®, Medtronic®, Sulzer®, and others. Polymer leaf type valves are not yet in use, but several companies are in the process of developing such products. A new type of prosthesis based on artificial polymer materials such as polyurethane, nylon and Dacron® are being considered.
Tissue-based valves do not require ongoing usage of anti anticoagulation drugs. However, they tend to degenerate over time and may require replacement within 10 to 15 years, necessitating a further operation. There is a wide range of biologically based replacement valves made of natural valves or composed of biological materials. The membrane comprising the one way valve leaflets is traditionally made of a native heart valve or pericardium harvested from different species, such as bovine, equine and porcine. These are assembled and marketed by well-known companies such as Edwards Lifesciences®, Medtronic®, Sulzer®, Sorin®, and others.
Mitral valve replacement may be performed robotically or manually. Surgical valve replacement or repair is often a demanding operation as it requires cardiopulmonary bypass and it can expose patients, especially elderly ones, to many risks.
A large variety of percutaneous or transcutaneous medical procedures are currently being developed and practiced. For example, transcatheter procedures are known for replacement of aortic and pulmonary heart valves. These procedures, which are performed under local anesthesia in the cardiac catheterization lab, rather than by cardiac surgery, offer tremendous benefits to these patients. According to such approaches, the valve is inserted on a delivery device similar to a catheter or a sheath and then implanted in the desired location via access through a large blood vessel such as the femoral artery, for example. It involves making a very small perforation in the patient's skin such as in the groin area to access the femoral artery. This minimally invasive option is usually safer than open heart surgery, and recovery times are typically shorter.
Minimal invasive transcatheter Mitral repair procedure may be accessed using different approaches for instance transeptal or transfemoral or transapical approaches. In the transapical approach, a small surgical incision is made and a catheter or a sheath is inserted between the ribs and into the apex of the beating heart, and the valve is manipulated through the sheath or catheter into the implantation site. In the transfemoral approach, a sheath or a catheter is inserted through the femoral artery and the valve is advanced retrogradely through the sheath to the implantation site in the arterial side. In the transeptal approach, the right atrium is accessed via the vena cava which may be accessed through the subclavian vein. Then the left atrium is accessed by piercing the interatrial septum, perhaps using a mechanical or laser tool.
In transcatheter procedures, access to the native diseased valve is limited. Hence removal of the old valve is in many cases impossible and the prosthetic valve is implanted on top of or over the old valve, as described, for example, in U.S. Pat. No. 6,730,118, which is assigned to Edwards Lifesciences PVT Ltd.
To enable implantation of prosthetic replacement valves using a transcatheter approach, collapsible prosthetics have been developed. The folded or crimped profile of the prosthetic valve, directly influences the ability to insert the valve into the femoral artery or vein without causing trauma to the blood vessels whilst transporting the valve to the implantation site. Accordingly, a smaller profile allows for safer treatment of a wider population of patients.
The valve prosthesis remains folded or crimped until it reaches the proper location where it is expanded. Such crimping was once considered detrimental to leaflet structure, causing tears and calcification to leaflets; however these issues have largely been resolved. The transcatheter valve replacement approach is similar to the use of coronary stents that has been used successfully over the last few decades.
Typically the valve is constructed from a metallic frame, referred to as a stent, and a membrane constructed from a one-way valve mounted onto the stent.
The stent typically comprises a substantially cylindrical tube or mesh sleeve usually made from metal. The design of the stent material permits the stent to be radially crimped and expanded, while still providing sufficient rigidity such that the stent maintains its shape once it has been enlarged to a desired size.
Percutaneous heart valves are, similarly to stents, divided into two main types: self expandable valves and balloon expandable valves.
A shape memory alloy (SMA, smart metal, memory metal, memory alloy, muscle wire, smart alloy) is an alloy that “remembers” its original, set shape, and which returns to that shape after being deformed.
The three main types of shape memory alloys are the copper-zinc-aluminium-nickel, copper-aluminium-nickel, and nickel-titanium (NiTi) alloys also known as nitinol.
NiTi alloys are fully biocompatible and may be used in prosthetics and surgical procedures. They are, however, generally expensive. They change from austenite to martensite upon cooling. The transition from the martensite phase to the austenite phase is only dependent on temperature and stress, and, in contradistinction to most phase changes are time-independent, as there is no diffusion involved. It is the reversible diffusionless transition between the two phases that allow the special properties to arise. An additional material characteristic of these SMA materials is super-elasticity, self expandable valves are made of super elastic materials which may have an elastic allowable strain characteristic of around 8% as opposed to the typical elastic (i.e. reversible) strain of steels and stainless steels which is up to 1%. Valves fabricated from such shape-memory alloys may be compressed to a very small diameter which can be kept in the small configuration within a constraining tube, and, once released from the constraining tube, they expand to a final larger diameter. For example a crimped diameter of such a valve or stent may be 5 to 6 mm while the expanded diameter can be 24-32 mm. The environmental temperature influences the process of reducing and expanding the stent using the shape memory thermal characteristic.
Balloon expandable valves are constructed from metals that have plastic deformation properties such as stainless steel or cobalt chromium alloy. They can be transported to the implantation position in the small crimped diameter configuration and then radially expanded by inflating a balloon, thus opening the valve to its working configuration.
The membrane constructing the one way valve is traditionally made of pericardium harvested from different species, mainly bovine. However, they can be also made of artificial material such as polyurethane, nylon, Dacron or even a thin membrane of Nitinol. \The membrane may also be made of a harvested native valve such as a porcine aortic heart valve.
Another important concern of valve replacement is securing the prosthesis within its proper location. Typically, the primary attachment mechanism of the prosthetic valve to the native valve is friction, which is generated by radial contact forces between the stenotic valve and the frame of the valve. Thus proper sizing is an important factor for securing the attachment of the prosthetic valve to the native valve to provide good sealing, and, to avoid, for example, paravalvular leaks.
Structural and physical parameters assist the stable anchorage of a prosthetic valve over the native valve. For example, the prosthetic aortic valve is naturally located in a circular tubular blood vessel, the aorta, and is anchored to a strong fibrous construction around the whole circumference. Additionally in most cases the diseased native aortic valve is calcified and thus rigid, further assisting the stable anchoring of the prosthetic aortic valve. Replacement methods for aortic valves may be unsuitable for replacing mitral valves which differ therefrom, both anatomically and geometrically (morphologically). The mitral valve is ellipse shaped, non-tubular and has an uneven circumference. Its leaflets are inserted on the circumference of the mitral annulus. The inner, or anterior leaflet, is in continuity with the aortic annulus and the fibrous trigones and is made of a constructive fibrous tissue. However, the outer, posterior leaflet is continuous with the posterior ventricle wall, which can dilate in some cases since it is not connected to the cardiac skeleton. Positioning and expanding a transcutaneous circular prosthetic valve (e.g. transcutaneous prosthetic aortic valve) within the opening of the ellipse shaped diseased mitral valve may result in inadequate sealing of the mitral valvular annulus, thereby resulting in severe regurgitation. Furthermore, a circular valve deployed in a standard fashion will have poor anchoring and the valve is prone to detach and migrate from its position, to the detriment of the patient.
The valve leaflets are connected to the anterolateral and posteromedial papillary muscles by chordae tendineae. Primary chordae are attached to the free edge of the valve leaflet, and secondary chordae are attached to the ventricular surface of the leaflets. These chordae are important for the proper structure and function of the mitral valve and implanting a prosthetic replacement valve over the native mitral valve could potentially sever the chordae. If the chordae are severed, then the ventricular wall is no longer anchored to the valve apparatus and the tethering effect of the chordae is lost. As a result, left ventricular wall stress increases and left ventricular function deteriorates.
Several prosthetic valves are known. See for example WO 98/29057 and U.S. Pat. No. 5,411,552, U.S. Pat. No. 6,168,614 and U.S. Pat. No. 5,840,081. A method for deploying a prosthetic valve device in body ducts has been described in U.S. Pat. No. 7,510,575. An apparatus for replacing a diseased AV valve using a minimally invasive, percutaneous approach has been described in U.S. Pat. No. 7,611,534, where the apparatus has at least one anchoring portion which is anchored in an opening extending from the atrial chamber.
The main disadvantage of the methods for valve implantation described in the aforementioned patents is that they are not suitable for mitral valve replacement, mainly due to lack of or insufficient or cumbersome anchorage of the apparatus, and their application tends to risk continued regurgitation, i.e. blood backflow from left ventricle to left atrium upon systole. Furthermore, the prosthetic valve apparatus is inserted over the native valve and thus there is increased risk of rupturing chordae tendineae or damaging the healthy leaflet. Thus, there is a long-felt need for a method which provides proper anchorage for mitral valve prosthesis, securing it in its proper location after implantation without severing the chordae tendineae and which also prevents paravalvular regurgitation.
It is an object of the present invention, to provide a method for percutaneously implanting a prosthetic mitral valve apparatus to replace the function of a dysfunctional or diseased mitral valve without severing the chordae tendineae. It is a further object of the invention to provide a solution for paravalvular leakage and regurgitation.